Cryosynthesis of Co-Crystals of Poorly Water-Soluble Pharmaceutical Compounds and Their Solid Dispersions with Polymers. The “Meloxicam–Succinic Acid” System as a Case Study

Co-crystals of pharmaceutical compounds are widely used to improve the properties of drug formulations, such as dissolution behavior, bioavailability, or tabletability. The main methods of their synthesis include co-crystallization from solution, melt, or cogrinding. Only a few examples have been documented when co-crystals have been obtained by freeze-drying, namely, in systems where the components of a target co-crystal had similar aqueous solubilities. This work illustrates the potential of freeze-drying for obtaining pharmaceutical cocrystals when the solubilities of individual components differ drastically. Co-crystals of a model system—meloxicam and succinic acid—could be obtained both as a pure crystalline phase and forming a solid dispersion with a polymeric carrier. We show that even for pharmaceutical compounds with very low aqueous solubility, co-crystals with well-soluble coformers can be successfully produced under well-optimized conditions of cooling and subsequent freeze-drying. The rate of...